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Ace seamer Vernon Philander has been ruled out of the second test, starting at St Georges Park on Friday.
The world's second-ranked bowler, and first test man of the match, has a strained left hamstring and the diagnosis has a seven to 10-day recovery period.
Philander, who took five wickets in his first 25 balls to set up the first test demolition at Cape Town last week, is replaced by burly Rory Kleinveldt, who will play his third test, and first at home.
Kleinveldt will present his own problems for the New Zealand batsmen, and impressed with one three-wicket burst against Australia at Adelaide late last year, but with all due respect he's no Philander.
A nervous Kleinveldt delivered 12 no balls on debut at Brisbane, and again overstepped 11 times at Adelaide.
Pakistan arrive for a three-start series, which starts on February 2 and that is Philander's targeted return date.
"We feel it's unlikely that he'll recover in time," South Africa's manager, Mohammad Moosajee, who is also a medical doctor, said.
"With the Pakistan series less than a month away, it's not worth the risk of aggravating the injury."
In 13 tests, Philander has taken a staggering 74 wickets at a cost of just 17 runs each. He has now missed three tests in his first 16 opportunities through injury - a knee problem counted him out of the Boxing Day test against Sri Lanka in 2011, and he sat out the Adelaide test recently with back spasms.
South Africa's spinner, Robin Peterson characterised the loss of Philander as "a huge blow".
"He's been a stalwart in the test team, his performances speak for themselves, he's a critical part of our bowling unit," he said.
That said, Philander and Kleinveldt are team-mates at the Cape Cobras, fed off each other in terms of planning and taking wickets, and Peterson said much would be expected from Kleinveldt.
An indication of the relentless nature of the Dale Steyn/Philander/Morne Morkel/Jacques Kallis pace quartet at Cape Town was revealed by New Zealand's batting coach Bob Carter today.
He said it was not until halfway through the 14th over of New Zealand's second innings that a ball was bowled down the legside - taking into account New Zealand's wretched 19.2-over first innings, that's 32.3 overs into the match before a stray delivery came a batsman's way.
In a bid to search for morsels of comfort, Carter pointed to the third morning when century-maker Dean Brownlie and BJ Watling batted through all but the last three minutes of that two-hour session.
"They are the No 1 and have been relentless wherever they've played," Carter said.
"For an hour and 57 minutes we made them change their game plan. They brought on Peterson early; Philander changed ends. That's part of the mental plan we have to have. It's a great opportunity for us to go at them."
Carter said the South African bowling philosophy towards New Zealand hadn't surprised them.
"We know how they'd come at us. They were going to bowl short, try and put some fear into us, then bowl full," he said.
"That's how they bowled in their last two series against England and Australia. That was their pattern. So we knew what to expect."
Coping with it in reality, however, presented significant hurdles.
Carter noted a disturbing trend on the last three overseas test tours. Having been well beaten by India in Hyderabad in August, New Zealand fought back in Bangalore a few days later, albeit still in a losing cause.
Then after being dusted in Galle in November, they bounced back to beat Sri Lanka by 167 runs at Colombo in the second test of that rubber.
"It's a little bit worrying that we've had a bit of a trend.
"It's a case that again we've got to pick it up, work hard and mentally prepare ourselves for this battle," he said.
Peterson, for one, expects more from New Zealand on his home ground, which he suspects would be the one New Zealand players would be most at ease on.
"New Zealand showed in the second half of the Cape Town game that they put up a bit of a fight," he said.
"That's the nature of Kiwis. What they might have lacked in a player pool they make up for in their determination and a bit of guts they put on the park.
"I'd expect them to be a little more at home at St Georges than anywhere else in the country."
- David Leggat of the NZ Herald in Port Elizabeth